Alpha-1-antitrypsin immunoreactivity in gastric carcinoid

Alpha-1-antitrypsin (AAT) was demonstrated in tumour cells in three out of five cases of gastric carcinoma showing the histological characteristics of carcinoid tumour. It was also detected in normal stomach mucosa, but was not found in 10 cases of adenocarcinoma of intestinal or mucous cell type. The AAT-positive tumour cells were argyrophilic, PAS-positive and were negative for pancreatic and gastric hormones. These findings suggest a possible malignant proliferation of alpha-1-antitrypsin-containing cells in the stomach.     

Immunohistologic study of intestinal antigen beta-2-MA in gastric tumors

Immunologic techniques were used to examine localization of the intestinal antigen beta-2-MA in 87 cases of malignant gastric tumors and 25 cases of non-neoplastic diseases of the stomach. The antigen was identified in 46.4% of gastric carcinomas. The presence of the antigen was not found to be related to a histological type of cancer. The beta-2-MA antigen was detected in the areas of intestinal metaplasia alone in 48% of the cases and in combination with malignant tumors in 50.9%. The antigen was found to be more common in the mucosa adjacent to those of diffuse cancer than in the mucosa located around cancer of intestinal type (p less than 0.01). beta-2-MA is one of the antigens showing intestine-differentiated cells in a number of gastric tumors and may be useful for immunological studies of gastric neoplastic types.     

The expression of Lewis antigens in neoplasms of the gastrointestinal tract

The indirect immunoperoxidase technique has been used to demonstrate Lea and Leb antigens in paraffin sections of both morphologically normal gastric and colonic mucosae and their neoplastic counterparts. Expression differed in various regions of the gastrointestinal tract: Leb occurred most frequently in the stomach and Lea most frequently in the colon. Coexpression of Lea and Leb occurred in only 5% of cases of normal mucosa, in 65% of gastric carcinomas and in 82% of carcinomas of the colon. Furthermore, 75% of cases of intestinal metaplasia in gastric mucosa and 30% of tubular adenomas, 50% of villous adenomas and 70% of tubulovillous adenomas in the colon co-expressed Lea and Leb antigens. In this study, the expression of Lewis antigens in carcinoma was found to differ from that of adjacent normal mucosa in 95% of cases of gastric carcinoma and 100% of cases of colonic carcinoma. The differences were shown by antigen acquisition and/or deletion. Similar changes were shown in 88% of cases of intestinal metaplasia in gastric mucosa, 20% of cases of tubular adenomas and 57% of cases of villous and tubulovillous adenomas of colon.     

Detection of the epithelial membrane antigen in patients with varying status of the gastric mucosa using monoclonal antibodies

To study how the normal gastric mucosa develops chronic gastritis, gastric ulcer or cancer, biopsies from 103 patients with non-tumor gastric diseases and operative specimens from 12 patients with stomach carcinoma were examined for epithelial antigen (EA). In the peroxidase-antiperoxidase reaction performed on paraffin-embedded and cryostat sections of the gastric mucosa, monoclonal antibodies (MAb) to antigens located on the membranes of fatty breast milk globules were employed, which had been presented by the Department of Biomedical Sciences, Tampere University (Finland). The MAb 111C12-identified antigenic determinant was found to occur in 12.8% of the nonmalignant gastric mucosa examined and 48% of the stomach carcinoma one. The detection of EA is not characteristic of the given portion of the gastric mucosa in carcinoma.     

Neural invasion in gastric carcinoma.

AIMS--To determine whether neural invasion in advanced gastric cancer is of clinicopathological significance. METHODS--The study population comprised 121 cases of primary advanced gastric carcinoma. Two paraffin wax embedded blocks taken from the central tissue slice in each primary tumour were used. For definitive recognition of neural invasion, immunostaining for S-100 protein was applied to one slide; the other slide was stained with haematoxylin and eosin. RESULTS--Neural invasion was recognised in 34 of 121 (28%) primary gastric carcinomas. There were significant differences in tumour size, depth of tumour invasion, stage, and curability between patients with and without neural invasion. The five year survival rates of patients with and without neural invasion were 10 and 50%, respectively. Multivariate analysis, however, demonstrated that neural invasion was not an independent prognostic factor. CONCLUSIONS--Neural invasion could be an additional useful factor for providing information about the malignant potential of gastric carcinoma. This may be analogous to vessel permeation which is thought to be important, but is not an independent prognostic factor.     

Clinicopathologic evaluation of CDw75 antigen expression in patients with gastric carcinoma

Situated on mature B lymphocytes, CDw75 antigen is a sialylated carbohydrate epitope generated by the enzyme beta-galactosyl alpha-2,6-sialyltransferase. Although CDw75 antigen expression was found to be correlated with aggressive behaviour of tumour cells in gastric adenocarcinomas, its prognostic role still remains unknown. The objective of this study was to determine the value of CDw75 antigen expression as a marker of the metastatic potential and prognosis of gastric adenocarcinomas. CDw75 antigen expression was evaluated immunohistochemically in 64 tumours and their nodal metastases. The correlation was analysed between CDw75 antigen expression and selected clinicopathological variables, including survival. Positive staining was detected in 31 cases. Non-neoplastic gastric mucosa was consistently negative. CDw75 expression was correlated with larger tumour size (p<0.006), infiltrative growth pattern (p<0.044), advanced stage (p<0.0006), and positive lymph nodes (p<0.0003).The overall survival rate of patients with CDw75 expression was 28%, which was significantly worse than that of patients without CDw75 expression (53%) (p<0.0005). Multivariate analysis showed that CDw75 expression was an independent prognostic indicator, together with the growth pattern of the tumour. These results indicate that immunohistochemical detection of CDw75 antigen expression may be a good indicator of metastatic potential and of prognosis in patients with gastric carcinomas.     

胃癌组织HLA－I类和DR分子免疫组化研究

本文应用免疫组化法对６４例胃癌、癌旁组织和６例胃溃疡大致正常胃粘膜冰冻和石蜡切片进行了染色．结果表明，正常胃粘膜和癌旁胃粘膜上皮细胞ＨＬＡ－Ｉ类分子表达阳性，其着色较均一，ＨＬＡ－ＤＲ染色均阴性．胃癌细胞Ｉ类分子表达缺失（２７／６４例），与癌旁上皮比较差异显著（Ｐ＜０．０１）。粘液细胞癌和低分化癌Ｉ类分子缺失率显著高于高分化癌（Ｐ＜０．０２５）．此外，发生肿瘤转移的病例Ｉ类分子缺失率（１２／１５例）显著高于无转移组（１／５例，Ｐ＜０．０２５）．ＤＲ分子在癌组织表达阳性，其阳性率高达５３．１％（３４／６４例）．低分化癌ＤＲ分子阳性率亦显著高于高分化癌和中分化癌，未分化癌ＤＲ分子阳性率亦显著高于高分化癌（Ｐ＜０．０１～０．０５）．提示（１）ＨＬＡ－Ｉ类分子表达缺失可能与癌细胞逃避宿主免疫监视发生润浸生长和转移有关；（２）分化程度不同的癌组织ＨＬＡ－Ｉ类分子表达差异显著，提示癌细胞分化可能影响Ｉ、Ⅱ类分子表达和肿癌抗原呈递；（３）ＨＬＡ－Ｉ类和ＤＲ分子表达异常可能是上皮恶性转变的标志之一．     

T (Thomsen–Friedenreich) antigen and other simple mucin-type carbohydrate antigens in precursor lesions of gastric carcinoma

In a previous report we suggested that T antigen appeared to be associated with gastric carcinoma. To verify this hypothesis and characterize the pattern of expression of simple-mucin type carbohydrate antigens (Tn. sialyl-Tn and T before and after neuraminidase) in normal gastric mucosa and precursor lesions of gastric carcinoma, we studied the mucosa adjacent to 100 cases of gastric carcinoma, gastric biopsies of 60 dyspeptic patients, eight adenomatous polyps and eight hyperplastic polyps. The expression of the antigens was more related to the cell type and underlying lesions than to the coexistence of carcinoma. The most distinctive findings concerned intestinal metaplasia, dysplasia and hyperplastic lesions. In intestinal metaplasia, Tn was found mostly in columnar cells and sialyl-Tn in goblet cells. T was more prevalent in incomplete intestinal metaplasia than in complete. A high prevalence of sialyl-Tn expression and cell membrane immunoreactivity for T antigen, similar to those previously found in gastric carcinomas, were observed in three adenomatous polyps, one hyperplastic polyp, five cases of adenomatous dysplasia in the neighbourhood of intestinal carcinomas and four cases of marked foveolar hyperplasia, three of which were from the mucosa adjacent to diffuse carcinomas. We conclude that adenomatous and hyperplastic lesions share with gastric carcinomas features of aberrant glycosylation, namely the cell membrane expression of T antigen.     

The value of a study of the mucosubstances in rectal biopsies from patients with carcinoma of the rectum and lower sigmoid in the diagnosis of premalignant mucosa

One hundred and twenty-one rectal biopsies from 99 patients with carcinoma of the rectum or lower sigmoid colon were investigated using a high iron-diamine-Alcian blue technique for sulphated and non-sulphated acid mucins. It was found that in normal rectal mucosa sulphomucins are the main carbohydrate component of the goblet cell mucin. This normal ;mucous pattern' changes in the ;transitional' mucosa (histological normal mucosa adjacent to carcinoma) where there is an increase of non-sulphated acid mucins concomitantly with a decrease or absence of sulphated groups in 60 to 90% of the cases according to the type of tumour. The same type of changes in mucus were observed in the ;transitional' mucosa surrounding adenomatous polyps and papillary adenomas; they were not marked in areas around carcinoma in situ and not observed in the metaplastic polyps. These changes seem to be in direct relationship to the grade of differentiation and invasiveness of the tumour.The histochemical changes in the mucins seem to be in favour of a malignant potential in the so-called neoplastic polyps.The high iron diamine-Alcian blue, because of its ;specificity', consistent results, and easy technique is recommended for routine use together with haematoxylin and eosin staining in the diagnosis of premalignant changes.     

转录因子Snail及黏附分子E-cadherin在胃癌中的表达及意义

目的探讨转录因子Snail及黏附分子E—cadherin在胃癌中的表达及意义。方法采用免疫组化sP法检测96例胃癌组织和80例癌旁组织中Snail、E—cadherin的表达,分析两者在不同组织类型与分化程度胃癌中的表达,以及与临床病理因素之间的关系。结果胃癌组织E—cadherin的阳性率（37．5％）显著低于癌旁组织（100％）（P〈0．05）,E—cadherin的表达与胃癌不同分化程度、组织学类型、浸润深度、淋巴结转移、临床分期及远处转移有关（P〈0．05）。胃癌组织Snail阳性率（83．3％）显著高于癌旁组织（41．25％）（P〈0．05）,Snail的表达与胃癌不同分化程度、组织学类型、浸润深度、淋巴结转移及远处转移有关（P〈0．05）。胃癌组织中E—cadherin与Snail的表达呈负相关（P〈0．05）。结论E—cadherin蛋白低表达与Snail蛋白高表达可能是胃黏膜恶性转变以及胃癌发生浸润转移的重要生物学标志。联合检测E—cadherin及Snail对预测胃癌浸润转移有重要意义。     

Immunohistologic study of the localization of organ-specific antigens of the stomach and intestine and carcinoembryonic antigen in normal and pathologically altered stomach tissues

Localization of organospecific gastric and intestinal antigens, as well as of carcinoembryonic antigen (CEA) was studied by an indirect immune peroxidase method on the sections of fetal stomach, normal definitive stomach, gastric mucosa with features of superficial and deep gastritis, enterolysis and dysplasia, as well as in gastric tumours. Normally, pepsinogen was found to localize in zymogen cells and to disappear in enterolysis and dysplasia of gastric mucosa. Intestinal antigen is absent from the normal mucosa, but is found in all the cases with enterolysis and dysplasia. CEA is most specific for dysplasia of gastric epithelium. In cancers of intestinal type pepsinogen was found in 54%, intestinal (colonic) antigen in 37.5%, CEA in 62.5%. In diffuse type cancers pepsinogen was absent, intestinal antigen was found in 76.9%, CEA in 92% of tumours.     

Association of Helicobacter pylori with HLA-DR antigen expression in gastritis.

AIMS: To assess the association between Helicobacter pylori-associated gastritis and HLA-DR antigen (class II antigen) expression. METHODS: Fifty endoscopic gastric biopsy specimens were studied for the presence of H pylori, degree and type of inflammation, and for HLA-DR antigen expression in the epithelium. The cases were chosen to represent different categories: inflamed gastric mucosa with (n = 13) and without (n = 20) H pylori, and non-inflamed mucosa (n = 17). RESULTS: The antigen was aberrantly expressed in the antral mucosal epithelium in 11 of 12 cases (92%) with acute-on-chronic gastritis when H pylori was also present. It was present in the antrum in only seven of 18 H pylori negative cases (39%) with acute-on-chronic/chronic gastritis. One of three cases of acute gastritis and three of seven cases of chronic gastric erosions (non-inflamed category) showed positive staining. Generally, there was more staining in the antral than body mucosa and in the surface/foveolar epithelium than in the glands. No aberrant HLA-DR antigen expression was found in the 10 cases of normal gastric mucosa examined. CONCLUSIONS: These findings suggest that H pylori may have a role in the induction of class II HLA antigen expression in chronic gastritis and lend support to the view that these organisms may be responsible for part of the inflammatory response.     

胃癌及其癌前病变中细胞凋亡及其调控基因的表达

目的:通过观察胃癌及其癌前病变中细胞凋亡及其调控基因p53、bcl-2、c-myc的表达,探讨其在胃癌恶性转化进程中的作用。方法:利用DNA末端标记技术(TdT-mediateddUTP-biotinnickendlabeling,TUNEL法)和免疫组织化学(streptavidin/peroxidase,S-P法),原位观察了46例胃癌、20例癌前病变、24例正常粘膜中的凋亡细胞和p53、bcl-2、c-myc的表达。结果:癌前病变和胃癌中凋亡指数显著高于正常粘膜(P＜0.01),癌前病变组高于胃癌组(P＜0.01)。p53、bcl-2、c-myc蛋白在胃癌中阳性率分别为60.9%、67.4%、73.2%,均高于正常粘膜组(P＜0.01);在癌前病变中3种蛋白阳性表达率分别为40%、95%、58.8%(P＜0.01)。胃癌中p53、bcl-2蛋白阳性细胞凋亡指数分别低于阴性组(P＜0.05),c-myc蛋白阳性组细胞凋亡指数高于阴性组(P＜0.01)。结论:细胞凋亡调控异常在胃癌发生中可能起重要作用。p53、bcl-2蛋白分别抑制细胞凋亡,c-myc蛋白在胃癌中促进细胞凋亡。     

Carcinoplacental alkaline phosphatase in malignant and premalignant conditions of the human digestive tract

Summary The presence of carcinoplacental alkaline phosphatase (CP Alk P) was demonstrated in the cells of malignant and premalignant states of the human stomach, colon and rectum using the immunoperoxidase technique.It was shown to be present in 7 out of 18 carcinomas of stomach and 7 of 17 cases of carcinoma of colon and rectum. In the putative premalignant states it was demonstrated in 4 of 15 cases of intestinal metaplasia associated with gastric carcinoma, and 9 of 12 tubulovillous adenomas of colon. However, it was also demonstrated in 5 of 8 metaplastic polyps of colon which are not neoplastic and in 9 of 17 cases of intestinal metaplasia not associated with cancer of the stomach. It was not seen in normal gastric mucosa and only faintly in 1 of 11 samples of normal colon.CP Alk P has been shown to be a specific marker of malignancy in a wide range of human cancers when studied in sera from patients or in tissue culture of tumour cells. In this study however, although a statistical difference exists between normal and diseased tissue the marker appears as frequently in non-neoplastic states. It is concluded that CP Alk P is, in tissues, a marker of proliferative activity in cells, rather than neoplastic or malignant change.In this respect it is similar in some respects to carcinoembryonic antigen, but not other markers of placental origin such as pregnancy specific , glycoprotein.Senior Lecturer in Pathology, Flinders University of South Australia. Senior Staff Specialist in Pathology, Flinders Medical CentreProfessor of Pathology, Flinders University of South Australia. Head of Department of Histopathology, Flinders Medical Centre     

Adenosquamous carcinoma of the stomach: histological, histochemical and ultrastructural observations

The histochemical and ultrastructural features of an adenosquamous carcinoma of the stomach have been studied. Both the adenomatous and the squamous component of the tumour showed malignant characteristics. Elements which were considered as undifferentiated cells on light microscopy showed ultrastructural features of poorly differentiated squamous cells. No intermediate cells, sharing squamous and glandular aspects, were found by electron microscopical examination. The adenomatous component exhibited histochemical and ultrastructural features of the intestinal type of gastric carcinoma and the mucosa surrounding the tumour showed a colonic type of intestinal metaplasia. A possible histogenesis from a totipotential undifferentiated cell is considered.     

Loss of phenotypic expression is related to tumour progression in early gastric differentiated adenocarcinoma

AIMS : To evaluate the relationship between phenotypic expression and tumour progression as represented by macroscopic features, submucosal invasion and lymph node metastasis in early differentiated gastric adenocarcinoma. METHODS : One hundred and fifty-five cases of early gastric differentiated adenocarcinoma without any poorly differentiated components were studied. The mucosal and submucosal components of carcinomas and lymph node metastatic lesions were classified into four categories, gastric type (G-type), incomplete intestinal type (I-type), complete intestinal type (C-type) and unclassified type (U-type), based on the combination of the phenotypic expression of HGM (gastric foveolar epithelium), MUC 6 (gastric pyloric glands), MUC 2 (intestinal goblet cells) and CD 10 (small intestinal brush border). In addition, a new classification representing a phenotypic shift from mucosa to submucosa or from primary lesion to lymph node metastasis was established with the categories of preserved group (P-group), loss group (L-group) and acquired group (A-group). RESULTS : (1) In submucosal carcinoma, U-type was more common in the submucosa (39%) than in the mucosa (9%). (2) U-type was more common in the metastatic lesions (42%) than in the primary lesions (5%). (3) The submucosal component and lymph node metastatic lesions were classified as P-group in 48% and 43% of cases, respectively, and as L-group in 50% and 52% of cases, respectively. (4) Lymph node metastatic lesions comprising undifferentiated carcinoma were classified as L-group in 100% of cases. CONCLUSION : During the course of tumour progression, early differentiated adenocarcinoma at first tends to lose its phenotypic expression despite preserving its morphology, but subsequently morphological dedifferentiation occurs.     

Host response and tumour biological behaviour in the two histological types of gastric carcinoma

It appears that there is validity in categorizing gastric carcinoma into two histologic types, intestinal and diffuse. The local host tissue response in 92.5% of cases of the intestinal type of gastric carcinoma was of an exudative nature. Diffuse gastric carcinoma in 70% of cases incited a dense productive fibrosis. Pools of mucin and large number of 'signet-ring' cells were mostly encountered in the intestinal type of carcinoma. Applying Dukes' parameters the tumour was found to be more than three times more invasive in cases of diffuse carcinoma. The prognostic bearing of the two histologic types, different host tissue response, behaviour of the tumour in terms of mucous production and local extension are discussed and it is suggested that diffuse gastric carcinoma carries a worse prognosis than the intestinal type. Study of a larger series of cases and longer follow-up with controlled treatment is essential to confirm this assessment.     

Immunocytochemistry of malignant mesothelioma: OV632 as a marker of malignant mesothelioma.

In pleural or ascitic effusions the cytomorphological distinction of adenocarcinoma cells, reactive mesothelial cells, and malignant mesothelioma cells often causes a diagnostic dilemma. The value of immunocytochemistry was investigated on cytological smears of 24 well-established cases of malignant mesothelioma, a selected series of 31 metastatic adenocarcinomas, and 20 smears of patients without known malignancy. In these smears we scored the immunoreactivity with a panel of four monoclonal antibodies. In addition to antibodies for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), the monoclonal antibody MOC31 and the ovarian carcinoma specific antibody OV632 were incorporated in the panel. With none of these four antibodies was immunostaining of reactive mesothelial cells found. CEA- and MOC31-positive tumour cells were frequent in metastatic adenocarcinomas, but occurred rarely in malignant mesotheliomas. EMA-positive tumour cells were found in all metastatic adenocarcinomas (100 per cent) and in most malignant mesotheliomas (83 per cent). In addition to the expected reactivity of OV632 with ovarian carcinomas, 22 of 24 malignant mesotheliomas contained immunopositive tumour cells, while only a small proportion of non-ovarian adenocarcinomas reacted with this antibody. This selective staining of malignant mesothelioma cells, but not reactive mesothelial cells, with OV632 now permits the positive identification of malignant mesothelioma cells in male patients.     

MHC class I and II antigens on gastric carcinomas and autologous mucosa

The expression of HLA class I and II antigens was analysed in 30 primary gastric carcinomas, 27 autologous lymph node metastases and 25 autologous gastric mucosae. We used an immune alkaline phosphatase technique on cryostatic sections and mAbs directed against HLA class I monomorphic determinants, HLA-B locus-specific products and HLA-DR, -DP and -DQ molecules. In addition HLA class I genes were analysed in tumour tissue and compared by Southern blots with the RFLP from autologous mucosa using locus-specific HLA probes. Finally the infiltrating mononuclear cells were studied on gastric tumours and adjacent mucosa with mAbs defining CD4, CD8 and CD11b differentiation antigens. The results obtained showed that three out of 27 primary gastric carcinomas completely lack HLA-ABC antigens (10%). In addition, two primary tumours presented a variable expression. The remaining 22 tumours presented a homogeneous positive HLA class I expression. Interestingly, when the autologous mucosa was analysed, only 12 out 25 specimens were homogeneously stained with mAbs against HLA class I antigens, suggesting that this tissue may lack the expression of HLA antigens before becoming malignant. Indeed, the majority of the gastric carcinomas studied presented a higher HLA-ABC antigenic expression than autologous mucosa. Finally, the HLA expression observed in the primary tumour was similar to that observed in autologous metastases. As a second part of the study we have found a direct relationship between the expression of HLA-DR antigens in mucosa and the intensity of inflammatory infiltration. This relationship was not maintained in the tumour tissue. In the mucosa the CD4-positive T cell was the predominant lymphocyte, while it was CD8 in the HLA-DR-positive tumours. Finally the RFLP of class I genes did not show any differences in any of the cases when compared with autologous mucosa. We included in these studies DNAs from HLA class I-negative tumours, HLA positive and HLA-B-negative ones.